P-glycoprotein (P-gp) mediates the active transport of various substrates including xenobiotics, and it thus has a protective function in various cell types and tissues/organs including the intestinal epithelium. However, whether or not P-gp plays a positive role in the intestinal tumorigenesis is unclear. We have introduced disrupted alleles of the murine P-gp gene, mdr1a, into Apc(Min/+) mice...

Safingol is a lysosphingolipid protein kinase C (PKC) inhibitor that competitively interacts at the regulatory phorbol binding domain of PKC. We investigated the effects of safingol on antineoplastic drug sensitivity and PKC activity of MCF-7 tumor cell lines. Safingol treatment of 32P-labeled MCF-7 WT and MCF-7 DOXR cells inhibited phosphorylation of the myristoylated alanine-rich protein kina...

Methadone is a widely used substitution therapy for opioid addiction. Large inter-individual variability has been observed in methadone maintenance dosages and P-glycoprotein (P-gp) was considered to be one of the major contributors. To investigate the mechanism of P-gp's interaction with methadone, as well as the effect of genetic variants on the interaction, Flp-In™-293 cells stably transfect...

MDR1 P-glycoprotein (P-gp), the multidrug resistance-associated transmembrane transporter, is physiologically expressed by human peripheral immune cells, but its role in cell-mediated immunity remains poorly understood. Here, we demonstrate a novel role for P-gp in alloantigen-dependent human T cell activation. The pharmacologic P-gp inhibitor tamoxifen (1-10 microM) and the MDR1 P-gp-specific ...

Digoxin, a drug of narrow therapeutic index, is a substrate for common transmembrane transporter, P-glycoprotein, encoded by ABCB1 ( MDR1 ) gene. It has been suggested that ABCB1 polymorphism, as well as co-administration of P-glycoprotein inhibitors, may influence digoxin bioavailability. The aim of the present study was to evaluate the effects of ABCB1 gene polymorphism and P-gp inhibitor co-...

PURPOSE P-glycoprotein (P-gp) plays a major role in oral absorption of drugs. Induction or inhibition of P-gp by drugs contributes to variability of its transport activity and often results in clinically relevant drug-drug interactions. The purpose of this study was to investigate the effect of cetirizine, a second generation H1 antihistamine, on P-gp function and expression in vitro and in sit...

P-glycoprotein (P-gp) pumps a broad range of structurally diverse anti-cancer drugs out of cancer cells. Therefore, multi-drug resistance (MDR) in chemotherapy closely correlates with P-gp. However, how this single transport system recognizes different substrates remains unclear. In this study, we attempt to uncover the mechanism of substrate promiscuity of P-gp by atomistic molecular dynamics ...

P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp...

P-glycoprotein (P-gp) is thought to mediate the transport of anti-cancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype in tumor cells. However, the function of P-gp in normal tissues is still not well understood. We present evidence indicating that the active efflux of several structurally unrelated organic compounds is mediated by P-gp in multidrug-resistant KB (KB-C2...

Recent studies have suggested that overexpression of the multidrug transporter P-glycoprotein (P-gp) in the hippocampal region leads to decreased levels of antiepileptic drugs and contributes to pharmacoresistance that occurs in a subset of epileptic patients. Whether P-gp expression and function is affected in other brain regions and in organs that are involved in drug metabolism is less studi...